Recent studies have unequivocally demonstrated an important role of central catecholaminergic neurons in the hypotensive action of alpha-methyl-DOPA (alpha-MD). To produce hypotension and antihypertensive action, this amino acid has to be metabolized in these neurons to form alpha-methylnorepinephrine (alpha-methyl-NE, alpha-MNE). The question arises concerning the site and type of synaptic action of alpha-MNE, involved in the central control of blood pressure. This project is based on the hypothesis that alpha-MNE, formed in the catecholaminergic terminals of the descending bulbo-spinal pathways, modulates the activity of spinal sympathetic preganglionic neurons (SPGN), acting as a false neurotransmitter. Our preliminary study indicates that alpha-MNE applied by means of microiontophoresis produces a definite inhibitory effect on the activity of SPGN which is not related to the release of endogenous norepinephrine. This could be a most important factor in the central action of alpha-MD, regardless of the supraspinal effects, becasue spinal SPGN are the main central sympathetic output station. The purpose of this investigation is to: 1) analyze the inhibitory effects of alpha-MNE and alpha-methyldopamine, 2) to compare them with catecholamine neurotransmitters, 3) to analyze the specificity of these effects by using receptor antagonists, 4) to investigate the effects of monoamines and receptor antagonists on the activity of SPGN modulated by inhibitory and excitatory inputs to these neurons. This will provide a better understanding of the mechanism of antihypertensive action of alpha-MD. Experiments will be performed on cats anesthetized with a mixture of chloralose and urethane and immobilized with gallamine. SPGN will be identified with antidromic stimulation of the splanchnic nerves or white rami of the stellate ganglion. Metabolites of alpha-MD and neurotransmitters will be applied by means of microiontophoresis in the close vicinity of SPGN at various levels of the thoracic spinal cord.